Helicobacter pylori (H. pylori) is globally accepted as an important cause of gastritis in human, and evidence strongly shows an etiological role for H. pylori in gastric cancer and peptic ulceration. In this study, we determined the relationship between digestive diseases and the horB gene of H. pylori infection. Fresh antral biopsy specimens were obtained from 140 dyspeptic patients (67 men and 73 women; mean age 41.5, aged 19-63 years). They were examined for presence of the horB gene of H. pylori clinical isolates. Bacterial DNA content was extracted directly from the antral biopsy. Statistical analysis was performed with SPSS version 16.0. Prevalence of the horB gene in H. pylori isolated from patients with gastric cancer, gastric ulcer, gastritis and duodenal ulcer is (5/32) 15.6%, (4/25) 16%, (30/43) 70%, and (9/40) 22.5%, respectively. No significant relationship is observed between age, pathologic findings and gender factors with respect to the four digestive diseases (P > 0.05). In our examination, a significant association was observed between a horB positive genotype of H. pylori and the occurrence of gastritis; in support of the protective theory. Studies with a higher sample size in different countries of the world should be conducted to obtain a thorough assessment as to whether horB has a role in the progress of gastritis (protective effect) or not. Further tests should be carried out to determine the exact role of horB in infection of H. pylori.